α2-Adrenoceptor-mediated potassium currents in acutely dissociated rat locus coeruleus neurones

摘要

class="enumerated" style="list-style-type:decimal">The noradrenaline (NA)-activated response was investigated in neurones acutely dissociated from the rat locus coeruleus (LC) using nystatin-perforated, conventional whole-cell and inside-out patch recording modes under current- and voltage-clamp conditions.Under current-clamp conditions, NA hyperpolarized the LC neurones, abolishing the spontaneous action potentials. In voltage-clamp studies, NA induced an inwardly rectifying K⁺ current (INA) in a concentration-dependent manner with a half-maximum effective concentration of 2.2 × 10⁻⁷ m.INA was mimicked by the α2-agonist UK14304 but was inhibited by either the α2B/α2C antagonist ARC239 or the α1- and α2B/α2C antagonist prazosin, suggesting the contribution of α2B/α2C adrenoceptors.INA was inhibited by the intracellular application of GDPβS but fully activated by intracellular perfusion of GTPγS.In the inside-out recording mode, the application of GTP to the cytoplasmic side of the patch membrane markedly enhanced the open probability of the NA-activated single channels which represented the inwardly rectifying properties.These results indicate that the activation of α2B/α2C adrenoceptors coupled with GTP-binding protein directly activates the inwardly rectifying K⁺ currents in rat LC neurones, thus resulting in a decrease in the spontaneous firing activities.